This application is for funds to purchase the AB SCIEX QTRAP 6500 LC-MS/MS. This mass spectrometer has important performance features that distinguish it from other instruments available on campus and will enable us to perform high-end experiments for small molecule quantitation. The QTRAP 6500 offers state-of-the-art technology for quantitation, identification and structural analysis of small molecules. The main features we require include an electrospray ionization source, the APCI (Atmospheric pressure chemical ionization) source, an ultra high pressure liquid chromatography (uHPLC) interface, tandem mass spectrometry (MS/MS), the ability to perform in two operating modes (triple quadrupole and linear trap), and to switch quickly between them, a fast scan rate, the ability to perform quantitative measures of small molecules using selected reaction monitoring (SRM) and multiple reaction monitoring (MRM), and the ability to identify and quantify lipids. The QTRAP 6500 excels in each of these areas and thus is the instrument we have chosen. We will be able to solve challenging analytical problems and identify and quantify small molecules, such as lipids, hormones and environmental contaminants related to disease. Most of the users of the instrument are already collaborating together in projects, thus this will help solidify their scienific interactions. Seven major research projects, with NIH support, and one minor research project require the sensitivity and high throughput ability of the QTRAP 6500 mass spectrometer to answer important questions. We have developed preliminary data for many of the projects. Of the major projects, two involve analysis of contaminants and hydroxylated polyaromatic hydrocarbons (Denslow and Kane), three involve analysis of lipids (Clare-Salzler, Wood and Sabo-Attwood) and three require analysis of hormones or small intracellular molecules (Wood, James, Cohn). One minor user will contribute methods that can be shared by all. Many of the projects, but in particular the projects requiring lipidomics analyses, will require the SelexIONTM device. This feature uses the principle of differential mobility spectroscopy (DMS) to separate isobaric species. All of the projects will require selected reaction monitoring (SRM) or multiple reaction monitoring (MRM). All of these projects will result in better understanding of fundamental processes that lead to the potential treatment of diseases.